(P27-073-25) Role of Methyl Nutrients in Metabolic Programming of Glucose Homeostasis, Glucagon-Like Peptide 1 and Gut Microbiota in Wistar Rat Offspring

Objectives: The gastrointestinal tract is a source of gut peptides important for the regulation of glucose homeostasis and is colonized by diverse microorganisms. We have previously shown that the essential nutrient choline when supplemented during pregnancy can increase insulin sensitivity in Wistar rat offspring. This study was expanded to determine the role of prenatal supplementation of choline and its oxidized product betaine in glucose homeostasis and colon glucagon-like peptide 1 (GLP-1) concentrations, and whether the gut microbiota can predict metabolic outcomes in offspring.

Methods: Pregnant Wistar rats were fed an AIN-93G diet and randomly assigned to either 0.25% w/w choline from choline bitartrate (CB), 0.25% betaine anhydrous (BA) or no supplementation (untreated control) in drinking water. All offspring were fed a high-fat diet for 12 weeks post-weaning. Glucose response to a glucose load was measured at 10 weeks post-weaning. The distal section of the colon tissue was harvested at 12 weeks post-weaning. Colon GLP-1 and gut microbiota profiles were determined by enzyme-linked immunosorbent assay and 16S rRNA sequencing, respectively.

Results: Glucose response to a glucose load as assessed by incremental area under the curve was lower in female and male offspring of CB dams and BA dams (p < 0.05 for females; p < 0.01 for males) consistent with higher colon GLP-1 concentrations (p < 0.001 for females; p < 0.01 for males). Significant beta-diversity measures were found using unweighted UniFrac distances among diet groups (PERMANOVA p < 0.01 for females and males). A supervised machine learning classifier indicated that the gut microbiota was a predictor of colon GLP-1 concentrations (r = 0.34; p < 0.05) with Sporosarcina, Glutamicibacter, Corynebacterium, Enteractinococcus, Romboutsia, Akkermansia, Lactococcus and Adlercreutzia as top features of importance.

Conclusions: Supplementation of choline or betaine during pregnancy contributes to glucose homeostasis and greater colon GLP-1 concentrations predicted by gut microbiota. Our findings highlight the potential for harnessing metabolic benefits through dietary components as modulators of host-gut interactions.

Funding Sources: NSERC-DG; UofG Team Building Grant; URA to EMP; CIHR CGS-M to GVS; CIHR CRC II to CEC